Environmental Chemical Exposure May Contribute to Uterine Cancer Development

Abstract

Tetrabromobisphenol A (TBBPA), a widely used flame retardant, caused uterine tumors in rats. In this study, TBBPA was administered to male and female Wistar Han rats and B6C3F1/N mice by oral gavage in corn oil for 2 years at doses up to 1,000 mg/kg. TBBPA induced uterine epithelial tumors including adenomas, adenocarcinomas, and malignant mixed Müllerian tumors (MMMTs). In addition, endometrial epithelial atypical hyperplasia occurred in TBBPA-treated rats. Also found to be related to TBBPA treatment, but at lower incidence and at a lower statistical significance, were testicular tumors in rats, and hepatic tumors, hemangiosarcomas (all organs), and intestinal tumors in male mice. It is hypothesized that the TBBPA uterine tumor carcinogenic mechanisms involve altered estrogen levels and/or oxidative damage. TBBPA treatment may affect hydroxysteroid-dehydrogenase-17β (HSD17β) and/or sulfotransferases, enzymes involved in estrogen homeostasis. Metabolism of TBBPA may also result in the formation of free radicals. The finding of TBBPA-mediated uterine cancer in rats is of concern because TBBPA exposure is widespread and endometrial tumors are a common malignancy in women. Further work is needed to understand TBBPA cancer mechanisms.

A comparative assessment of human exposure to tetrabromobisphenol A and eight bisphenols including bisphenol A via indoor dust ingestion in twelve countries

“…Additionally, immunotoxicity, neurotoxicity and interference of cellular signal pathways have been reported for TBBPA (Mariussen and Fonnuma, 2003;Pullen et al, 2003;Strack et al, 2007). In a recent study, TBBPA-mediated uterine cancer has been shown in rodents exposed under laboratory conditions (Dunnick et al, 2015).…”

Biochar and activated carbon act as promising amendments for promoting the microbial debromination of tetrabromobisphenol A

“…The increasing occurrence of TBBPA in environmental samples, including aquatic sediments, agricultural soils, and wastewater sludge (Liu et al, 2016), has raised some concerns regarding wildlife (Chen et al, 2016), and human health as TBBPA has been shown to disrupt thyroid and estrogen regulative functions, cause liver and kidney damage, and increase risks of uterine cancer in mammals (Dunnick et al, 2015). In wastewater sludge, TBBPA concentrations as high as 732 mg kg −1 dry weight have been recorded (Li et al, 2016), and wastewater effluents discharging into receiving waters still contain measurable levels of TBBPA (up to 18.8 ng L −1 ; Liu et al, 2016).…”

Disruption of estrogen homeostasis as a mechanism for uterine toxicity in Wistar Han rats treated with tetrabromobisphenol A

“…The safety of TBBPA is of concern based on effects on the endocrine system in animals and a recent study reporting carcinogenic activity in TBBPA-treated rats and mice (Dunnick et al, 2015). Studies conducted in vitro indicate that TBBPA competes with thyroxine (T4) for binding to transthyretin (TTR), inhibits binding of triiodothyronine (T3) to thyroid hormone receptors (TR), affects gene or protein expression of TR and peroxisome proliferator-activated receptors (PPARs), and may bind to PPARγ (Hamers et al, 2006; Kitamura et al, 2002; Meerts et al, 2000; Riu et al, 2011).…”